Background: Mitral valve prolapse syndrome (MVPS) and MASS phenotype (MASS) are Marfan-like syndromes that exhibit aortic dilatation and mitral valve prolapse. Unlike inMarfan syndrome(MFS), the presence of ectopia lentis and aortic aneurysm preclude diagnosis of MVPS and MASS. However, it is unclear whether aortic dilatation and mitral valve prolapse remain stable in MVPS or MASS or whether they progress like in MFS. Methods: This retrospective longitudinal observational study examines clinical characteristics and long-term prognosis of 44 adultswithMVPS orMASS (18 men, 26 women aged 38±17 years) as compared with 81 adults with Marfan syndrome (MFS) with similar age and sex distribution. The age at final contact was 42 ± 15 years with mean follow-up of 66 ± 49 months. Results: At baseline, ectopia lentis and aortic sinus aneurysmwere absent inMVPS andMASS, and systemic scores defined by the revised Ghent nosology were lower than in MFS (all P b .001). Unlike in MFS, no individual with MVPS and MASS developed aortic complications (P b .001). In contrast, the incidence of endocarditis (P = .292), heart failure (P=.644), andmitral valve surgery (P=.140)was similar in all syndromes. Cox regression analysis identified increased LV end-diastolic (P = .013), moderate MVR (P = .019) and flail MV leaflet (P = .017) as independent predictors of mitral valve surgery. Conclusions: The study provides evidence thatMVPS andMASS areMarfan-like syndromeswith stability of aortic dilatation butwith progression of mitral valve prolapse. Echocardiographic characteristics of mitral valve disease rather than the type of syndrome, predict clinical progression of mitral valve prolapse.